IFN-gamma and IL-10 are two cytokines that play a critical role in dictating the balance between host resistance and immunopathology in parasitic and bacterial infections. In this years work, we studied at the single cell level the requirements for the generation of IFN-gamma producing Th 1 CD4+ Tcells in mice stimulated with T.gondii or M.avium while following at the same time the expression of IL-10 and Th2 cytokines. Although IL-12 deficient mice infected with irradiated T.gondii tachyzoites or with M.avium developed only a small fraction of the IFN-gamma producing CD4+ T cells displayed by equivalently exposed wild-type mice, no compensating expansion of IL-4, IL-5 producing Th2 cells (expressed minimally in the wild type mice) was observed in these KO animals. Similarly, IL-10 expression, which occurred in 10-50% of the IFN-gamma producing CD4+ T cells, was not reduced in either IL-12 deficient mice or STAT-6 KO mice that are unresposive to the Th2 differentiating cytokine IL-4. Together our findings indicate that the IFN-gamma, IL-10 dominated Th1 cytokine secretion pattern of CD4 T cells induced by intracellular pathogens such as toxoplasma and mycobacteria is not dependent on their initial induction of IL-12 but on other factors instrinsic to these infectious agents.
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